Abstract
Background: Lactoferricin peptide (LP) has been reported to control cancer cell proliferation. NF-κB interacting lncRNA (NKILA) is a tumor suppressor in several cancers.
Objective: We aimed to explore the potential function of the truncated LP (TLP) in the prevention of cervical cancer cell proliferation.
Methods: Bioinformatics analysis via PPA-Pred2 showed that 18-aa N-terminus of truncated lactoferricin peptide (TLP18, FKCRRWQWRMKKLGAPSI) shows higher affinity with nuclear factor kappaB (NF-κB) than LP. The effects of LP and TLP18 on cervical cancer cells SiHa and HeLa and the related mechanisms were explored by investigating NF-κB and lncRNA-NKILA.
Results: TLP18 shows an inhibitory rate up to 0.4-fold higher than LP on the growth of cervical cancer cells (P<0.05). NKILA siRNA promoted cell growth whether LP or TLP18 treatment (P<0.05). TLP18 treatment increases the level of lncRNA-NKILA and reduces the level of NF-κB up to 0.2-fold and 0.6-fold higher than LP (P<0.05), respectively. NKILA siRNA increased the levels of NF-κB, cleaved caspase-3, and BAX (P<0.05). TLP18 increased apoptotic cell rate up to 0.2-fold higher than LP, while NKILA siRNA inhibited cell apoptosis cell growth even LP or TLP18 treatment.
Conclusion: Truncated Lactoferricin peptide controls cervical cancer cell proliferation via lncRNA- NKILA/NF-κB feedback loop.
Keywords: Long non-coding RNA, cervical cancer, truncated lactoferricin peptide, lncRNA-NKILA, nuclear factor kappaB (NF-κB), cell proliferation.
Graphical Abstract
[http://dx.doi.org/10.1056/NEJMe1814034] [PMID: 30379600]
[http://dx.doi.org/10.1056/NEJM199904153401509]
[http://dx.doi.org/10.1016/j.clinthera.2016.02.007] [PMID: 26926322]
[http://dx.doi.org/10.1007/s00428-005-1264-9] [PMID: 15856292]
[http://dx.doi.org/10.1139/bcb-2016-0175] [PMID: 28165293]
[http://dx.doi.org/10.1007/s00018-005-5370-2] [PMID: 16261255]
[http://dx.doi.org/10.1016/j.jconrel.2010.03.007] [PMID: 20307599]
[http://dx.doi.org/10.3892/ol.2021.12766] [PMID: 33986866]
[http://dx.doi.org/10.3892/ol.2020.12338] [PMID: 33363614]
[http://dx.doi.org/10.2147/OTT.S255067] [PMID: 33116605]
[http://dx.doi.org/10.1016/j.biopha.2019.109616] [PMID: 31881485]
[http://dx.doi.org/10.3892/ol.2019.10524] [PMID: 31423284]
[http://dx.doi.org/10.1371/journal.pgen.1008325] [PMID: 31430288]
[http://dx.doi.org/10.1177/1533033820960747] [PMID: 33143574]
[http://dx.doi.org/10.1186/s13046-017-0518-0] [PMID: 28049532]
[http://dx.doi.org/10.1186/s12859-018-2448-z] [PMID: 30442086]
[http://dx.doi.org/10.1016/j.bbrc.2009.08.083] [PMID: 19699713]
[http://dx.doi.org/10.1042/bj3490135]
[http://dx.doi.org/10.1074/jbc.M113.475657] [PMID: 23720754]
[http://dx.doi.org/10.1016/j.yexmp.2013.07.006] [PMID: 23892223]
[http://dx.doi.org/10.1016/j.joen.2015.11.012] [PMID: 26806398]
[http://dx.doi.org/10.1182/blood-2010-10-306571] [PMID: 21212284]
[http://dx.doi.org/10.5937/jomb0-27128] [PMID: 33776564]
[http://dx.doi.org/10.1111/jcmm.16213] [PMID: 33377616]
[http://dx.doi.org/10.1016/j.biopha.2021.111369] [PMID: 33582452]
[http://dx.doi.org/10.1016/j.nut.2020.110935] [PMID: 32799043]
[http://dx.doi.org/10.1097/CAD.0000000000000890] [PMID: 32568829]
[http://dx.doi.org/10.1097/CAD.0000000000001073] [PMID: 33929997]
[http://dx.doi.org/10.1093/jpp/rgab049]
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.08.012] [PMID: 32846215]
[http://dx.doi.org/10.1016/j.pathol.2018.03.003] [PMID: 29935727]
[http://dx.doi.org/10.1111/j.1349-7006.2011.02061.x] [PMID: 21834855]
[http://dx.doi.org/10.1002/cncr.24743] [PMID: 19890957]
[http://dx.doi.org/10.1111/j.1525-1438.2007.00872.x] [PMID: 17316355]
[http://dx.doi.org/10.12688/f1000research.6400.1] [PMID: 26069731]
[http://dx.doi.org/10.18632/oncotarget.11528] [PMID: 27613832]
[http://dx.doi.org/10.1016/j.yexmp.2020.104490] [PMID: 32663487]
[PMID: 31934087]
[http://dx.doi.org/10.1186/s12885-021-07995-2] [PMID: 33750326]
[http://dx.doi.org/10.1002/jcb.27300] [PMID: 30171719]
[http://dx.doi.org/10.1002/jcla.23317] [PMID: 32249459]
[http://dx.doi.org/10.26355/eurrev_201905_17913] [PMID: 31173281]
[http://dx.doi.org/10.3892/etm.2020.8752] [PMID: 32765657]